EPHA8

EPH receptor A8, the group of Sterile alpha motif domain containing|EPH receptors

Basic information

Region (hg38): 1:22563488-22603595

Previous symbols: [ "EEK" ]

Links

ENSG00000070886 ∙ NCBI:2046 ∙ OMIM:176945 ∙ HGNC:3391 ∙ Uniprot:P29322 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPHA8 gene.

• Inborn genetic diseases (61 variants)
• not provided (9 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPHA8 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	2	4
missense			61	1	1	63
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					1	1
Total	0	0	61	3	4

Variants in EPHA8

This is a list of pathogenic ClinVar variants found in the EPHA8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-22569315-C-T		not specified	Uncertain significance (Nov 09, 2022)
1-22576287-G-A		not specified	Uncertain significance (Aug 10, 2021)
1-22576296-A-G		not specified	Uncertain significance (Feb 15, 2023)
1-22576334-G-A		not specified	Uncertain significance (Jan 26, 2022)
1-22576361-A-C		not specified	Uncertain significance (May 28, 2023)
1-22576406-A-C		not specified	Uncertain significance (Jan 22, 2024)
1-22576448-C-T		not specified	Uncertain significance (Mar 20, 2023)
1-22576460-G-T		not specified	Uncertain significance (Dec 14, 2022)
1-22576490-A-C		not specified	Uncertain significance (Nov 19, 2022)
1-22576499-A-G		not specified	Uncertain significance (Apr 19, 2023)
1-22576505-G-A		not specified	Uncertain significance (Feb 21, 2024)
1-22576517-T-C		not specified	Uncertain significance (Aug 30, 2021)
1-22576608-C-T		not specified	Uncertain significance (May 30, 2023)
1-22576686-A-G		not specified	Uncertain significance (Nov 13, 2023)
1-22576688-C-T			Benign/Likely benign (Nov 01, 2022)
1-22576763-C-G		not specified	Uncertain significance (Jul 12, 2023)
1-22576775-C-T		not specified	Uncertain significance (Jan 23, 2024)
1-22576799-A-G		not specified	Uncertain significance (Aug 08, 2023)
1-22576809-G-T		not specified	Uncertain significance (Oct 12, 2021)
1-22576817-C-G		not specified	Uncertain significance (Jul 06, 2021)
1-22576817-C-T		not specified	Uncertain significance (Jul 16, 2021)
1-22576863-G-A		not specified	Uncertain significance (Jun 21, 2023)
1-22586600-G-A		not specified	Uncertain significance (Jan 03, 2024)
1-22588880-C-T		not specified	Uncertain significance (Feb 26, 2024)
1-22588912-G-T		not specified	Uncertain significance (Dec 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPHA8	protein_coding	protein_coding	ENST00000166244	17	40031

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.83e-10	1.00	125665	0	83	125748	0.000330

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.707	642	694	0.924	0.0000493	6460
Missense in Polyphen		281	316.99	0.88646		2783
Synonymous	1.55	261	295	0.885	0.0000216	2099
Loss of Function	3.15	24	47.4	0.506	0.00000256	481

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000209
Ashkenazi Jewish	0.00	0.00
East Asian	0.00134	0.00131
Finnish	0.0000964	0.0000924
European (Non-Finnish)	0.000275	0.000264
Middle Eastern	0.00134	0.00131
South Asian	0.000672	0.000621
Other	0.000338	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor tyrosine kinase which binds promiscuously GPI- anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. The GPI-anchored ephrin-A EFNA2, EFNA3, and EFNA5 are able to activate EPHA8 through phosphorylation. With EFNA5 may regulate integrin-mediated cell adhesion and migration on fibronectin substrate but also neurite outgrowth. During development of the nervous system plays also a role in axon guidance. Downstream effectors of the EPHA8 signaling pathway include FYN which promotes cell adhesion upon activation by EPHA8 and the MAP kinases in the stimulation of neurite outgrowth (By similarity). {ECO:0000250}.
• Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;EPH-Ephrin signaling;Axon guidance;EPHA forward signaling (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• loftool: 0.421
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.21

Haploinsufficiency Scores

• pHI: 0.325
• hipred: Y
• hipred_score: 0.651
• ghis: 0.427

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.778

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Epha8
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype

Gene ontology

• Biological process: substrate-dependent cell migration;cell adhesion;transmembrane receptor protein tyrosine kinase signaling pathway;axon guidance;neuron remodeling;peptidyl-tyrosine phosphorylation;regulation of cell adhesion;neuron projection development;regulation of cell adhesion mediated by integrin;positive regulation of MAPK cascade;positive regulation of phosphatidylinositol 3-kinase activity;protein autophosphorylation;ephrin receptor signaling pathway;cellular response to follicle-stimulating hormone stimulus
• Cellular component: plasma membrane;integral component of plasma membrane;early endosome membrane;neuron projection;receptor complex
• Molecular function: transmembrane receptor protein tyrosine kinase activity;GPI-linked ephrin receptor activity;transmembrane-ephrin receptor activity;ATP binding